This study shows that pretreatment with both SS-31 and SS-20 significantly reduced myocardial lipid peroxidation and infarct size in ischemia-reperfusion injury, and suggests that the cardioprotective properties of 2',6'-dimethyl-tyrosine-D-Arg-Phe-Lys-NH2 was primarily mediated by its antioxidant properties. As SS-20 does not scavenge reactive oxygen species, it most likely reduces reactive oxygen species production during ischemia-reperfusion.

In patients with residual hypertriglyceridemia despite statin treatment, a combination of ω-3 fatty acids and rosuvastatin produced a greater reduction of TGs and non-HDL-C than rosuvastatin alone. Further study is needed to determine whether the advantages of this lipid profile of ω-3 fatty acids actually leads to the prevention of cardiovascular event. ClinicalTrials.gov identifier: NCT03026933.

. Growth factor-mediated reversal of senescent dysfunction of ischemia-induced cardioprotection. Am J Physiol Heart Circ Physiol 290: H525-H530, 2006. First published September 23, 2005 doi:10.1152/ajpheart.00470.2005.-Based on the role of tumor necrosis factor-␣ (TNF-␣) in ischemic preconditioning (IPC) and the age-associated loss of both TNF-␣-induced platelet-derived growth factor-AB (PDGF-AB)-mediated cardioprotection and IPC-mediated cardioprotection, we hypothesized that targeting of PDGF-AB-based pathways would restore cardioprotection by IPC in the aging heart. To study this, IPC was induced in 4-and 24-mo-old F344 rats. Sections of young hearts isolated 1 day post-IPC revealed increased TNF-␣ compared with controls. In old rats, TNF-␣ was higher at baseline than IPC young rats and was not significantly altered after IPC. Treatment of old rats with PDGF-AB with vascular endothelial growth factor and angiopoietin-2 (a combination termed PVA), but not PDGF-AB alone, at the time of IPC decreased TNF-␣. In addition, when compared with young hearts, IPC induced greater apoptosis in the old hearts, which was decreased with PVA treatment but was markedly increased with PDGF-AB. To test the significance of these findings, additional rats underwent permanent coronary ligation 1 day post-IPC. IPC was cardioprotective in young rats [14 days postmyocardial infarction (MI), fractional shortening 29 Ϯ 6% vs. control MI 17 Ϯ 4%, P Ͻ 0.05; Masson's trichrome stain MI size: 13 Ϯ 2% vs. control MI 17 Ϯ 4% left ventricular area (LVA); P Ͻ 0.05]. In old rats, however, IPC reduced the post-MI 14-day survival (33% vs. controls 67%; P Ͻ 0.05). Treatment of IPC-aging rats with PVA, but not PDGF-AB-alone, reversed IPC-induced mortality (PVA-IPC-MI survival, 88%; PDGF-AB-IPC-MI, 14%) and reduced myocardial injury (fractional shortening: PVA-IPC, 31 Ϯ 1% vs. control MI, 21 Ϯ 6%, P Ͻ 0.05; MI size: PVA-IPC, 12 Ϯ 2% vs. control MI, 18 Ϯ 3% LVA, P Ͻ 0.05) and thus demonstrated that PDGF-AB-based pathways can reverse the senescent impairment in IPC-mediated cardioprotection.aging; myocardial infarction; preconditioning AGE-RELATED ALTERATIONS in tumor necrosis factor-␣ (TNF-␣) pathways may contribute to the increased risk of cardiac disease and more severe cardiovascular pathophysiology in the geriatric population. Specifically, the recent results from the ABC Health Study revealed that in persons over 65 yr of age, TNF-␣ is more predictive of future cardiovascular events compared with C-reactive protein (CRP) (5). Moreover, clinical studies of inflammatory markers have linked elevations in TNF-␣ with an increased incidence of congestive heart failure after myocardial infarction (25). These findings in conjunction with the age-related increases in TNF-␣ in the systemic circulation (3) as well as the coronary arteries (7) suggest that strategies targeted at the actions of TNF

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